Glutaminase in microglia: A novel regulator of neuroinflammation

•GLS is strongly associated with the pathogenesis of various neurological disorders.•GLS is a novel regulator of inflammation, besides a classic excitotoxicity inducer.•GLS activates microglia and macrophages presumably by disturbing cellular metabolism.•GLS enhances inflammatory microenvironment formation via promoting exosome release. Neuroinflammation is the inflammatory responses that are involved in the pathogenesis of most neurological disorders. Glutaminase (GLS) is the enzyme that catalyzes the hydrolysis of glutamine to produce glutamate. Besides its well-known role in cellular metabolism and excitatory neurotransmission, GLS has recently been increasingly noticed to be up-regulated in activated microglia under pathological conditions. Furthermore, GLS overexpression induces microglial activation, extracellular vesicle secretion, and neuroinflammatory microenvironment formation, which, are compromised by GLS inhibitors in vitro and in vivo. These results indicate that GLS has more complicated implications in brain disease etiology than what are previously known. In this review, we introduce GLS isoforms, expression patterns in the body and the brain, and expression/activities regulation. Next, we discuss the metabolic and neurotransmission functions of GLS. Afterwards, we summarize recent findings of GLS-mediated microglial activation and pro-inflammatory extracellular vesicle secretion, which, in turns, induces neuroinflammation. Lastly, we provide a comprehensive discussion for the involvement of microglial GLS in the pathogenesis of various neurological disorders, indicating microglial GLS as a promising target to treat these diseases.